This invention relates in general to the detection of enzymes or enzymatic substrates directly by measuring the thermal signals produced by their reaction on the surface of a pyroelectric material.
The detection and measurement of enzymes or enzyme substrates in biological fluids is a problem of considerable importance in the detection of disease conditions or the elucidation of metabolic pathways in animal and vegetable substances. Workers in this field have been challenged by the need to develop an analytical method or instrument that is sensitive and reliable as well as adaptable to the physical constraints that may be imposed upon an analytical technique to measure enzyme systems in biological fluids. Many approaches have been investigated, including the detection of temperature changes in the environment of an enzyme and substrate resulting from the heat of reaction between that pair. Others have tried to detect temperature changes with thermistors and other temperature sensing devices but the methods have lacked sensitivity. Pyroelectric gas sensors have been disclosed by Taylor, U.S. Pat. No. 3,861,879, and Zemel, U.S. Pat. No. 4,551,425. The Taylor invention is limited to a device for the detection of a particular gas and is specifically directed to the detection of carbon monoxide. The Zemel invention incorporates a heater in a pyroelectric substrate to desorb adsorbed substances and corrollates their detection from heat changes associated with change of state. Zemel also describes and claims application of his pyroelectric sensor for the detection of an enzyme or coenzyme by reaction with a corresponding enzyme or coenzyme bound to the sensor. The pyroelectric sensor of Zemel is found to possess less than desirable sensitivity. Pyroelectric sensors, such as those described by Zemel, experience shortcomings when the enzyme or coenzyme are insufficiently bound to the sensor or where the bonding process significantly deactivates the enzyme.
Workers in the field of enzyme or enzyme substrate detection have also been challenged by the problem of how to immobilize said enzyme or substrate on a detector without chemically deactivating either. Similarly, investigators have struggled with the problem of detecting enzyme substrate reactions using thermal sensors where the heat of the reaction between the enzyme and substrate is weak.
Nothing in the prior art satisfactorily discloses an operable pyroelectric sensor for enzyme detection or solves the problems discussed herein.